The purpose of these experiments is to examine mechanisms that regulate the circulation to the brain stem under normal and pathological conditions. Autoregulation of blood flow is more effective in brain stem than in cerebrum during changes in systemic pressure. Both metabolic and myogenic mechanisms may contribute to autoregulatory responses in the cerebrum, but the relative contribution of each is not clear. Using a new method, I propose to examine metabolic and myogenic autoregulatory responses in brain stem. Recent evidence suggests that the endothelium contributes to stretch induced myogenic responses of the basilar artery in vitro. Experiments are proposed to examine the role of the endothelium in autoregulatory responses of brain stem vessels. Acute hypertension damages arterioles and venules in the cerebrum. Pial artery pressure is higher in brain stem than cerebrum during acute hypertension, but the blood-brain barrier is protected in the brain stem because increases in pial venous pressure are attenuated. Experiments are proposed to determine whether arteries and arterioles in brain stem are protected during acute hypertension and to examine mechanisms that may contribute to this protection. I have observed recently that serotonin produces pronounced rhythmic contractions of the basilar artery in vivo. Studies are proposed to determine if these responses are 1) intrinsic or modulated by neural influences, 2) dependent on extracellular calcium, 3) modulated by production of prostaglandins, or 4) dependent on the presence of intact endothelium. The area postrema is a region which lacks a blood-brain barrier and which plays an important role in autonomic control of the circulation. Using a new method, I propose to examine effects of acute hypertension on microvascular pressure and permeability to large molecules in the area postrema. I have recently observed that circulating vasopressin selectively dilates large cerebral arteries. I also propose to determine whether vasopressin dilates large cerebral arteries reflexly and to test whether this reflex is initiated at the area postrema.